Skipjack Tuna ( Katsuwonus pelamis ) Dark Muscle Hydrolysate Ameliorates Hyperuricemia in Mice via Regulating Gut Microbiota and Serum Metabolism

Peptides have emerged as promising agents for ameliorating hyperuricemia (HUA), a condition that poses significant risks to human health. This study evaluated the HUA-alleviating potential of skipjack tuna dark muscle hydrolysate (STDH) in a mouse model of HUA induced by potassium oxonate (PO) and hypoxanthine (Hx). The results demonstrated elevated serum uric acid (SUA) levels, increased xanthine oxidase (XOD) activity in the serum and liver, and kidney and intestinal damage in HUA mice. Although the standard drug allopurinol (AP) effectively reduced SUA levels and lowered XOD activity in the serum and liver, it exacerbated kidney damage and caused significant weight loss. In contrast, STDH intervention not only significantly lowered SUA, serum creatinine (SCr), and blood urea nitrogen (BUN) levels but also inhibited XOD activity in serum and liver. Notably, STDH ameliorated renal and intestinal morphological damage, as evidenced by hematoxylin-eosin (HE) staining. Gut microbiome analysis further revealed that STDH normalized the HUA-associated elevation of the Bacteroidetes/Firmicutes ratio. Untargeted metabolomics identified STDH's regulatory effects on glycine, serine, and threonine metabolism; arginine and proline metabolism; and glycerophospholipid metabolism, with glutamine implicated as a key player in HUA pathogenesis. These findings demonstrate that STDH effectively alleviates HUA while avoiding adverse effects associated with conventional therapy, positioning it as a safe and cost-effective functional food candidate for HUA management.